CHEM 263

Oct 14, 2010

Reactions of Substituted Benzene – Continued How can Basic Brown be synthesized from toluene? (The process of figuring out what starting materials could be used to synthesize a target molecule is known as retrosynthesis). NH2

H2N

B

N

N

N

N

A

NH2

toluene Basic Brown

B

NH2

It is easier to make the bond to the two B rings than it is to make the bond to ring A. The following rings (one of A and two of B) could be used to synthesize basic brown: N

B

A 2Cl-

NH2

N

N

NH2

N

These could be synthesized from toluene by the following:

NO2

HNO3 H2SO4 NO2

Sn HCl

B

NH2 NaNO2 HCl or HONO

NH2

A and B will react with each other spontaneously to form basic brown.

N A

N

N

N

Lecture Outline 3: Alcohols, Ethers, Stereochemistry, Ketones, and Aldehydes Nomenclature of Alcohols Alcohols are compounds that have a hydroxyl group (-OH) bonded to a carbon atom (but not a carbonyl C=O). Alcohols can be thought of as organic derivatives of water in which one of the hydrogens is replaced by an organic group: H-O-H versus R-O-H. Alcohols occur widely in nature and have many industrial and pharmaceutical applications. Ethanol is one of the simplest alcohols, finding use as a fuel additive, an industrial solvent, and key ingredient in many beverages (beer, wine etc).

H3C

H2 C

O

H

Ethanol Naming Alcohols Alcohols are classified as primary (1°), secondary (2°), or tertiary (3°), depending on the number of organic groups bonded to the hydroxyl bearing carbon. H R

R

H OH

R

H

R

OH

R

R

primary alcohol (1°)

OH

secondary alcohol (2°)

tertiary alcohol (3°)

Simple alcohols are named using the IUPAC system as derivatives of the parent alkane, using the suffix ol: 1) Select the longest carbon chain containing the alcohol, and derive the parent name by replacing the -e ending of the corresponding alkane with –ol. 2) Number the alkane chain, beginning at the end closest to the hydroxyl group. 3) Number the substituents according to their position on the chain. For example: H3C OH

methanol or methyl alcohol or wood alcohol

OH

ethanol

OH

n-propanol or 1-propanol

OH

2-propanol or isopropanol

If there is more than 1 OH group: 2 OH’s diol (glycol) 3 OH’s triol 4 OH’s tetraol Some simple and widely occurring alcohols have common names that are accepted by IUPAC. For example: OH HO

OH

HO

ethylene glycol or 1,2-ethanediol (antifreeze) the freezing point is lower if mixed with water

OH

glycerol or 1,2,3-propanetriol or propane-1,2,3-triol a precursor to fatty acids (esters) is used for lubricants such as KY jelly

You need to know the following structures: OH

O OH OH

OH

phenol

OH

O

4-hydroxyphenol or p-hydroxyphenol or hydroquinone

quinone

catechol

A more difficult example is the name of the sex pheromone from the silk worm moth shown below.

OH

hexadeca-10Z,12Z-dien-1-ol The longest chain is 16 carbons long, which is a hexadecane. The -e ending is dropped, and replaced with –ol to become hexadecan-1-ol. There are two cis double bonds present at positions 10 and 12. This information allows the compound to be named a 10,12-diene. Putting the overall name together then gives hexadeca-10Z, 12Z-dien-1-ol. This molecule was discovered by Adolf Butenandt in 1959. The word pheromone comes from pherein (to carry) and horman (excitement)

Physical Properties of Alcohols and Acidity Look at the following comparisons: Name Formula Molecular Weight (g/mol) Boiling Point (° C) State (at room temp)

Methanol CH3OH 32 65 liquid

Ethane CH3CH3 30 -89 gas

Ethane has almost the same molecular weight as methanol. However, the boiling point is much lower than methanol. Similarly, propane has approximately the same molecular weight as ethanol, but the boiling point is significant lower than ethanol: Name Formula Molecular Weight (g/mol) Boiling Point (° C)

Ethanol CH3CH2OH 38 78.5

Propane CH3CH2CH3 44 -44.5

Why are the boiling points so different? Answer: Alcohols are polar and able to form hydrogen bonds.

Alcohols are strongly associated with each other both through dipole-dipole attraction (weaker intermolecular force) and hydrogen bonding (a stronger intermolecular force). The presence of the electronegative oxygen atom polarizes the bonds, and produce dipole moments. The basic oxygen atoms also form partial bonds to the acidic hydroxyl hydrogens of another molecule (shown as dotted line in the figure above). Together, these factors raise the boiling points of alcohols far above their parent alkanes, with the hydrogen bonding being the most significant and powerful factor.

Review from previous term, there are three fundamental non-covalent bonding forces: 1. Hydrogen bonding (occur with hydrogen attached directly to electronegative atoms such as O, N, or halogen). Linus Pauling described this. 2. Dipole-dipole interaction 3. London dispersion forces (temporary dipole interactions, which is the basis for hydrophobic forces). This is comparatively a weak intermolecular force on a per atom basis, but large hydrophobic (non-polar) sections of molecules interact strongly and can overcome hydrogen bonding between two atoms in the same molecules. Physical Properties: 1. The polarity of alcohols make them quite soluble in (or miscible with) water if the number of carbons on the alcohol is less than 4. Butanol and higher alcohols are still soluble in water, but no longer infinitely miscible (completely soluble at all concentrations) 2. The melting point and boiling point for an alcohol is higher than its parent alkane (as seen from our comparison above). 3. The density of alcohol is less than 1 g/cm3 (and hence less than water. If the given alcohol is not miscible with water (Carbons >4), it will be floating on top of water) Acidity Let’s review some basic definitions

HA is the conjugate acid of A-, and A- is the conjugate base of HA. The equilibrium constant, or acidity constant, Ka, for this reaction can be expressed as: Ka = [H+] [A-] / [HA] For example: the dissociation of methanol

Ka = [H+][CH3O-] / [CH3OH] = 10-16 The oxygen of the OH group in methanol is partially negative charged and the hydrogen is partially positively charged. The O-H bond is easy to break and it can break spontaneously. When methanol with OH is put in a solution of methanol with O-D (deuterium), the hydrogen will exchange rapidly against deuterium. By analogy with pH, we can define a quantity pKa, which is often used. pKa = -log Ka

Generally, the stronger the acid, the lower the pKa. The pKa value for methanol is 16, for water is 15.7 (know these values). Since the pKa value of water is less than methanol, the dissociation of methanol is harder than water and water is a stronger acid than methanol. Remember that the pKa and pKw for water are not the same. Kw = [H+][OH-], Ka = [H+][OH-]/(H2O] Examples:

The pKa value of methane is about 45. It is not acidic. What happens when we replace the carbon with nitrogen, a heteroatom?

The pKa value of ammonia is 36, which is 9 orders of magnitude (109) more acidic than methane. This is because the nitrogen atom is more electronegative than carbon and able to stabilize the negative charge better. However, ammonia is still a very weak acid. The acidity of ammonia (NH3) should not be confused with the acidity of the ammonium ion (NH4+) which has a pKa of 9.26. Based on pKa values, is oxygen more or less electron withdrawing than nitrogen? Answer: Oxygen is more electron withdrawing. It has lower pKa value, able to stabilize the negative charge more. Name methane ammonia water hydrofluoric acid

Structure CH4 NH3 HOH HF

pKa 46 36 15.7 3.2

Less acidic

More acidic

Recall from last term, the stability of the conjugate anion determines the acidity of a compound. The more stabilized the anion is, more acidic the molecule is.

Name methanol ethanol isopropyl alcohol

Structure H3C-OH CH3-CH2-OH

tert-butanol

pKa 16 17 18 19

What do these pKa values mean in reactions?

Isopropanol dissociates to from isopropoxide anion and a proton. However, the dissociation constant is 1 x 10-18. Most of the molecules exist in the isopropanol form and only one part in 1018 is ionized. The equilibrium for this reaction lies far to the left. There are two alkyl groups attached to the central carbon bearing oxygen in isopropanol. The alkyl groups (methyls) donate electron density to that carbon (an inductive effect) that is already next to a negative charged center (O-). Since negative charges repel each other, the anion is less stabilized. Therefore, the anion is even less likely to form (less stabilized than if the alkyl groups (methyls) in isopropanol were missing. Methanol (pKa 16) is 100 times (102) more acidic than isopropanol, since it has only hydrogens (a less donating group) attached to the carbon bearing the negative oxygen in the corresponding anion)

For tert-butanol (tert-butyl alcohol), there are three alkyl groups (methyls) that donate electron density to the carbon next to a negative charged group (inductive donation of electrons destabilizes the anion). Therefore, it is less likely to dissociate (pKa 19) and the molecule is even less likely to ionize (less acidic).

Consider the example below:

Where does the equilibrium lie in the above reaction? Answer: It lies far to the right. The reaction of a stronger base (tert-butoxide) and a stronger acid (methanol) to a weaker base (methoxide) and weaker acid (tert-butanol) is very fast. Example:

Phenol has a pKa value of 10 (given this information, you should immediately recognize that it is more much acidic (about 6 orders of magnitude) than water (pKa 15.7) and methanol (pKa 16) since it has lower pKa value). As phenol is more acidic, this means that its conjugate anion is more stable. The phenoxide anion is stabilized through resonance (shown above). It has 4 resonance forms, and therefore, more ability to spread the negative charge and be stabilized. Where does the equilibrium lie for ionization of phenol to phenoxide and a proton (H+) ? Answer: It lies far to the left (not ionized). Even though phenol is 106 more acidic than water, its pKa of 10 tells you that the acidity constant is 10-10 or that only one part in 1010 is ionized, the rest exists as phenol with H attached to oxygen. Equilibriums will lie to the side with the weaker acid and weaker base

Example: Weaker base

Stronger acid Stronger base +

Weaker acid +

NaOH

O-

OH

H2O

Na+

Acidity of other alcohols Cl

NO2 NO2

OH

OH

phenol pKa = 10

cyclohexanol pKa = 18

OH

OH

4-chlorophenol pKa = 9.3

4-nitrophenol pKa = 7

NO2

NO2

O2N

O2N OH 2,4-dinitrophenol pKa = 4.5

NO2 OH

2,4,6-trinitrophenol picric acid pKa = 0.5

Next class, we will rationalize some of these pKa values.

OH 3-nitrophenol pKa = 9.3